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The role of de novo mutations in the development of amyotrophic lateral sclerosis
- Publication Year :
- 2017
-
Abstract
- The genetic basis combined with the sporadic occurrence of amyotrophic lateral sclerosis (ALS) suggests a role of de novo mutations in disease pathogenesis. Previous studies provided some evidence for this hypothesis; however, results were conflicting: no genes with recurrent occurring de novo mutations were identified and different pathways were postulated. In this study, we analyzed whole-exome data from 82 new patient-parents trios and combined it with the datasets of all previously published ALS trios (173 trios in total). The per patient de novo rate was not higher than expected based on the general population (P = 0.40). We showed that these mutations are not part of the previously postulated pathways, and gene-gene interaction analysis found no enrichment of interacting genes in this group (P = 0.57). Also, we were able to show that the de novo mutations in ALS patients are located in genes already prone for de novo mutations (P < 1 × 10(−15)). Although the individual effect of rare de novo mutations in specific genes could not be assessed, our results indicate that, in contrast to previous hypothesis, de novo mutations in general do not impose a major burden on ALS risk.
- Subjects :
- 0301 basic medicine
Male
Mutation rate
medicine.medical_specialty
Population
Biology
medicine.disease_cause
Article
03 medical and health sciences
0302 clinical medicine
Mutation Rate
Databases, Genetic
Protein Interaction Mapping
Exome Sequencing
Genetics
medicine
Humans
Genetic Predisposition to Disease
Protein Interaction Maps
Amyotrophic lateral sclerosis
education
Genetics (clinical)
Exome sequencing
Alleles
Genetic Association Studies
education.field_of_study
Mutation
C9orf72 Protein
Whole Genome Sequencing
Amyotrophic Lateral Sclerosis
medicine.disease
030104 developmental biology
Disease Pathway
Amino Acid Substitution
Case-Control Studies
Medical genetics
Female
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....2bfccc465bf0a6e799444c617dff4b90